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The NIMH Conte Center on "Dopamine Dysfunction in Schizophrenia"

Anissa Abi-Dargham, MD

The NIMH Conte Center on ”Dopamine Dysfunction in Schizophrenia” is organized to test the central hypothesis that striatal dopaminergic hyperactivity during development leads to prefrontal cortical dopamine dysfunction in schizophrenia and the cognitive deficits that characterize the disorder. Investigators in this Center have observed that: 1) the striatal dopaminergic excess in schizophrenia is greatest in the associative striatum, 2) the associative striatum receives convergent input from associative and limbic frontal cortical regions, rendering it crucial for integration of affective and cognitive processes, 3) striatal D2 receptor overexpression during development in mice results in frontal cortical dopamine alterations, prefrontal cortical dysfunction, as evidenced by irreversible learning deficits, as well as motivational and social deficits. The Center includes studies in humans, patients with schizophrenia and healthy volunteers, transgenic mice with abnormal dopamine D2 signaling, and non-human primates, to assess the effects of abnormal dopaminergic transmission on the rest of the circuitry and the resulting cellular and behavioral expression.

Our new perspective on a key alteration in this illness, which is dopamine dysfunction, and the set of mechanistic studies we are conducting in order to test it, will lead to new and better understanding of the disorder. This in turn may lead to preventive or therapeutic strategies that can be developed based on this new understanding.